The work relates to understanding the biochemical events associated with the normal function of the thyroid and to pathological conditions of the thyroid, such as Graves' disease. The work continues to support the hypothesis that alterations in ion fluxes are important early events, as well as primary actions of thyrotropin and pharmacologic agents. Since the previous studies on the effect of thyrotropin on iodide transport, the work has evolved in several directions. (i) Inositol phosphate production has been linked to iodide efflux and calcium mobilization induced by thyrotropin and norepinephrine through Alpha adrenergic receptor activation. (ii) Thyrotropin and norepinephrine stimulated iodide efflux has been related to the metabolism of arachidonic acid via the liposygenase or epoxigenase pathway; and to thyroglobulin iodination and thyroid hormone formation. The mechanism of iodide fluxes in thyroid cells have been further characterized and the roles of intracellular pH and iodide as regulators of iodide transport has been described. Studies of thyroidal transport have been extended to lysosomal transport of tyrosine and thyroid hormones. These collaborative studies have extended our understanding of the complex metabolism of NaI to thyroglobulin and thyroid hormone release. Antiidiotypic antibodies to the thyrotropin receptor have been produced. Preliminary studies suggest that these antibodies can be used to define the spectrum of antibody activities found in patients with Graves' disease, and to determine the molecular structure of the thyrotropin receptor.